Medical Research Society
12 p
42
HICROALBUHINURIA IS A POWERFUL PREDICTOR OF
VASCULAR DISEASE IN NON-DIABETIC SUBJECTS - THE
ISLINGTON DIABETES SURIIEY
JS Yudkin, RD Forrest and CA Jackson
44
ALBUMIN EXCRETION RATE AND PLASMA RENIN ACTIVITY IN
INSULIN DEPENDENT DIABETES MELLITUS.
MJ O'DONNELL, N LAWSON AND AH BARNETT.
Departments of Medicine and Clinical Chemistry, East
Birmingham Hospital, Birmingham, B9
Academic Unit of Diabetes & Endocrinology,
Whittington Hospital, London N19 5NF, England
SST, England.
Plasma Renin Activity (PRA) may playa role in the modification of blood pressure and renal haemodynamics.
The relationship between urinary albumin excretion
and vascular disease was studied in 187 subjects
aged over 41l selected from 11184 cases attending a
diabetic screening project.
Urinary albumin
excretion rate (ABR) exceeded 2llug/min in 3 of 13
newly diagnosed diabetics (23.1%) and 16 of 171
non-diabetics (9.4%) (P=Il.2).
There was a weak
relationship between AER and both systolic and
diastolic blood-pressure (r s=Il.18,P=Il.1l2 and
r s=Il.16,P=Il.1l3 respectively).
Coronary heart
disease, defined as major and minor ECG changes,
angina or a history of myocardial infarction, was
found in 54 of 164 (32.9%) SUbjects with AER
<21lug/min and 14 of 19 (73.7%) wi th ABa >2Ilug/min
(OR 5.71l, 95% CI 1.95-16.65). Peripheral vascular
disease, defined by an ankle:brachial systolic
pressure ratio of <1l.91l in either leg, was present
in 16/165 (9.7%) SUbjects with AER <2Ilug/min and
8 of 18 (44.4%) with AER >2Ilug/min-(OR 7.44, 95%
CI 2.57-21.57).
Logistic regression analysis,
i nc Lud i nq diabetes, impaired glucose tolerance,
systolic and diastolic blood-pressure, smoking,
age, gender, ethnic origin and body mass index,
demonstrated the independence of this relationship
between ABR >2Ilug/min and coronary heart disease
(OR 6.13, 95% CI 1.82-21l.64) and peripheral
vascular disease (OR 5.97, 95% CI 1. 78-21l.1l7).
Microalbuminuria is a powerfUl risk factor for
vascular disease in non-diabetic subjects.
43
HYPERGLYCAEMIA AT THE ONSET
RELATES TO SHORT-TERM MORTALITY
OF
STROKE
JS Gill, SK Gill, DG Beevers.
University Department of Medicine, Dudley Road
Birmingham BI8 7QH.
Hospital,
The relationship between the fasting blood glucose taken within
24 hours of admission to hospital and subsequent mortality was
studied in 230 patients with stroke aged below 70 years. In 80
patients, the glycosylated haemoglobin was measured to study
the relationship of the admission glucose to the previous
glycaemic state. The results demonstrated that the majority of
patients with fasting hyperg;lycaemia (FBS >8.0 mmol/I) were
previously diabetic (96%) and 'stress' hyperglycaemia was a rare
event (4%). Patients were followed for at least 2.5 years (range
2.5-4.0) after ictus and deaths recorded. Results were analysed
using Cox's regression model for predictors of survival. Fasting
blood glucose at admission was a determina:rt of short-term
mortality «30 days after admission) (Chi =29.6, p<O.OOO I,
exp(coefficient)=l.l). The glycosylated haemoglobir was related
to mortality Over 30 days after ictus (Chi =4.8, p<0.05,
exp(coefficient)=1.2). The level of the admission blood glucose
correlated with the neurological score (r=-0.3, p<O.OOOI). Animal
studies suggest that hyper glycaemia at the onset of induction of
cerebral infarction results in more extensive neurological damage
than when the animal is normoglycaemic. It is possible that
cerebral lactic acidosis resulting from anaerobic metabolism of
the elevated blood and cerebral glucose during stroke has
adverse effects upon the degree of neurological deficit and
subsequent mortality.
High and low levels of PRA have been reported in diabetic
patients with or without hypertension and/or diabetic
nephropathy (DN). We studied 73 type I (insulin dependent)
patients for PRA, diastolic blood pressure (DBP) and
urinary albumin excretion rate (AER). No patient was
taking a dru~ affecting PRA and none had serum creatinine
>400 ~ol 1-. AER and PRA were measured by radioimmunoass~~.
53 patients had normoproteinuria (AER <22 1mc g
min ), 11 microproteinuria (20 <AER_f200 mg m1n ) . and
7 macroproteinuria (AER >200 mcg m1n ). PRA was s1gnifica~rly ~ycreased in the microproteinuric (2.45 ± 1.69
nmoll
hr ) and macroproteinuric groups (2.79 ± 2.51
nmol 1-1 hr- l ) comp~red with normoproteinuric group (1.43
± 1.24 nmol 1-1 hr- , p<0.05) but with no significant
difference between the proteinuric groups. Mean diastolic
blood pressure was significantly higher in the microproteinuric group (76.92 ± 10.32 mm Hg) compared with the
normo (71.81 ± 7.37 and macro (71.14 ± 6.45 mm Hg)
"proteinuric groups (p<0.02).
DBP correlated with AER but
not PRA in the proteinuric patients (macro r
=
0.89,
p<O.OOI, micro r = 0.37, p<0.05). Macroproteinuric
patients had greater mean disease duration (p<O.OOI) but
were not significantly older.
Conclusions:
PRA is elevated in early DN even in the
absence of renal impairment.
PRA does not correlate with
DBP or AER in proteinuric type I (insulin dependent)
patients.
~
EFFECT OF AGE ON EXTRACELLULAR DIGESTION OF
FIBRONECTIN BY NEUTROPHILS
A. Chamba, S. L. Hill, R. A. Stockley and
D. Burnett
The Lung Immunobiochemical Research Group, The
General Hospital, Steelhouse Lane, Birmingham
Neutrophils digest extracellular connective
tissue in vitro because of secretion of elastase
and Cathepsi n 13".
Thi s may be important in
producing tissue damage in chronic lung diseases
(Lancet, 1987; ii: 1043).
Several functions of neutrophils, such as
superoxide release, decline with age (Exp.
Hematol; 1982; 11: 1005).
We have studied chemo
tactic response and extracellular proteolysis by
neutrophils from both young (19-28, n = 12) and
older healthy subjects (49-69 years, n
12).
Neutrophils were isolated from each subject
by Percoll density gradient centrifugation.
Extracellular proteolysis was assayed by
culturing cells on .zeI_ Fibronectin (FN) and
solubilised radioactive FN peptides were
measured in the supernatant.
Intracellular
levels of elastase and Cathepsin G were assayed
using specific chromogenic substrates.
The
chemotactic response to FMLP was measured using
modified blind-well chambers.
The neutrophils for the younger age group
digested more FN (mean 1.2; SD 0.53 pg) than
those of the older subjects (0.83; 0.45; p <
0.025).
The intracellular levels of elastase
(1.53; 1.0 }-lg/l0" cells) and Cathepsin G (1.0,
0.5 pg/tO· cells) were higher in cells from the
older SUbjects (p < 0.005 and < 0.025
respectively) than those from younger volunteers
(elastase mean 0.63, SD 0.32 pg/tO. cells;
Cathepsin G 0.61, 0.25).
No significant
difference was observed in the chemotactic
response of neutrophils from the two groups.
In summary extracellular proteolysis is a
neutrophil function that appears to decline with
age but this was not due to reduced amounts of
intracellular proteinase••
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